Show simple item record

dc.contributor.authorHettmer, Simone
dc.contributor.authorLin, Michael M.
dc.contributor.authorTchessalova, Daria
dc.contributor.authorTortorici, Sara J.
dc.contributor.authorCastiglioni, Alessandra
dc.contributor.authorDesai, Tushar
dc.contributor.authorMao, Junhao
dc.contributor.authorMcMahon, Andrew P.
dc.contributor.authorWagers, Amy J.
dc.date2022-08-11T08:09:19.000
dc.date.accessioned2022-08-23T16:26:23Z
dc.date.available2022-08-23T16:26:23Z
dc.date.issued2015-10-13
dc.date.submitted2015-12-03
dc.identifier.citationExp Cell Res. 2015 Oct 13. pii: S0014-4827(15)30113-0. doi: 10.1016/j.yexcr.2015.10.008. [Epub ahead of print] <a href="http://dx.doi.org/10.1016/j.yexcr.2015.10.008">Link to article on publisher's site</a>
dc.identifier.issn0014-4827 (Linking)
dc.identifier.doi10.1016/j.yexcr.2015.10.008
dc.identifier.pmid26460176
dc.identifier.urihttp://hdl.handle.net/20.500.14038/36555
dc.description.abstractHedgehog (Hh) pathway activation in R26-SmoM2;CAGGS-CreER mice, which carry a tamoxifen-inducible activated Smoothened allele (SmoM2), results in numerous microscopic tumor foci in mouse skeletal muscle. These tumors exhibit a highly differentiated myogenic phenotype and resemble human fetal rhabdomyomas. This study sought to apply previously established strategies to isolate lineally distinct populations of normal mouse myofiber-associated cells in order to examine cellular heterogeneity in SmoM2 tumors. We demonstrate that established SmoM2 tumors are composed of cells expressing myogenic, adipocytic and hematopoietic lineage markers and differentiation capacity. SmoM2 tumors thus recapitulate the phenotypic and functional hetereogeneity observed in normal mouse skeletal muscle. SmoM2 tumors also contain an expanded population of PAX7+ and MyoD+ satellite-like cells with extremely low clonogenic activity. Selective activation of Hh signaling in freshly isolated muscle satellite cells enhanced terminal myogenic differentiation without stimulating proliferation. Our findings support the conclusion that SmoM2 tumors represent an aberrant skeletal muscle state and demonstrate that, similar to normal muscle, myogenic tumors contain functionally distinct cell subsets, including cells lacking myogenic differentiation potential.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=26460176&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1016/j.yexcr.2015.10.008
dc.subjectDifferentiation
dc.subjectHedgehog signaling
dc.subjectIntratumoral cellular heterogeneity
dc.subjectSkeletal muscle
dc.subjectCancer Biology
dc.subjectCell Biology
dc.subjectDevelopmental Biology
dc.titleHedgehog-driven myogenic tumors recapitulate skeletal muscle cellular heterogeneity
dc.typeJournal Article
dc.source.journaltitleExperimental cell research
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/mccb_pubs/52
dc.identifier.contextkey7899992
html.description.abstract<p>Hedgehog (Hh) pathway activation in R26-SmoM2;CAGGS-CreER mice, which carry a tamoxifen-inducible activated Smoothened allele (SmoM2), results in numerous microscopic tumor foci in mouse skeletal muscle. These tumors exhibit a highly differentiated myogenic phenotype and resemble human fetal rhabdomyomas. This study sought to apply previously established strategies to isolate lineally distinct populations of normal mouse myofiber-associated cells in order to examine cellular heterogeneity in SmoM2 tumors. We demonstrate that established SmoM2 tumors are composed of cells expressing myogenic, adipocytic and hematopoietic lineage markers and differentiation capacity. SmoM2 tumors thus recapitulate the phenotypic and functional hetereogeneity observed in normal mouse skeletal muscle. SmoM2 tumors also contain an expanded population of PAX7+ and MyoD+ satellite-like cells with extremely low clonogenic activity. Selective activation of Hh signaling in freshly isolated muscle satellite cells enhanced terminal myogenic differentiation without stimulating proliferation. Our findings support the conclusion that SmoM2 tumors represent an aberrant skeletal muscle state and demonstrate that, similar to normal muscle, myogenic tumors contain functionally distinct cell subsets, including cells lacking myogenic differentiation potential.</p>
dc.identifier.submissionpathmccb_pubs/52
dc.contributor.departmentDepartment of Molecular, Cell and Cancer Biology


Files in this item

Thumbnail
Name:
Publisher version

This item appears in the following Collection(s)

Show simple item record